Introduction

Endoscopic mucosal resection (EMR) is standard of care for the management of large (≥20mm) non-pedunculated colonic polyps (LNPCPs). Its efficacy and cost effectiveness were limited by recurrence. Margin thermal ablation (MTA) to the post-EMR defect, has greatly mitigated this problem. However, electrocautery-related complications of delayed bleeding and perforation incur significant morbidity.
Cold snare polypectomy is effective and safe for the resection of small polyps with negligible recurrence rates. Application of cold snare resection to LNPCPs, while an attractive alternative, lacks high-quality evidence. We conducted a randomized trial to compare the efficacy and safety of cold EMR (C-EMR) to conventional (H-EMR).

Aims & Methods

A prospective single-centre randomized controlled trial was conducted at an Australian tertiary referral centre for flat, 15-50mm adenomatous LNPCPs referred for endoscopic resection. Prior to resection, eligible LNPCPs were randomly assigned to EMR using a dedicated cold snare or conventional H-EMR with margin thermal ablation (control). First surveillance colonoscopy (SC1) was conducted 6 months following resection. Scars were evaluated with high-definition white-light, narrow-band imaging and biopsy. The primary outcome was endoscopically visible and/or histologically confirmed recurrence at SC1. Secondary outcomes were clinically significant post-EMR bleeding (CSPEB), delayed perforation and technical success.

Results

931 LNPCPs were referred for endoscopic resection between November 2019-September 2023. 177 LNPCPs in 177 patients were randomized to either the C-EMR arm (n=87) or H-EMR arm (n=90). Treatment groups were equivalent with no significant difference in lesion size or technical success (86/87 (98.9%) vs 90/90 (100%); p=0.31). One C-EMR required conversion to H-EMR due to unexpected submucosal fibrosis. Following exclusions, 146 LNPCPs undertook SC1 (76 C-EMR, 70 H-EMR). 5 patients await surveillance. On intention to treat and per protocol analysis, recurrence was significantly greater in C-EMR (16/87, 18.4% vs 1/90, 1.1%; p<0.001 and 16/76, 21.1% vs 1/70, 1.4%; p<0.001 respectively). Significant deep mural injury (27/90 (30%) vs 0; p<0.001) and delayed perforation (1/90 (1.1%) vs 0; p=0.32) only occurred in the H-EMR group. CSPEB and intraprocedural bleeding were significantly greater in the H-EMR arm (7/90 (7.8%) vs 1/87 (1.1%); p = 0.034 and 12/90 (13.3%) vs C-EMR arm 1/87 (1.1%); p=0.002 respectively).

Conclusion

Compared to conventional H-EMR, C-EMR for flat, adenomatous LNPCPs, demonstrates superior safety with equivalent technical success. However, endoscopic recurrence is significantly greater for cold snare resection and is currently a limitation of the technique.

Disclosure

Michael Bourke: Research Support: Olympus Medical, Cook Medical, Boston Scientific
The remaining authors have no financial, professional, or personal conflicts of interest to disclose

Introduction

EMR is the standard of care for the management of large (≥20mm) non-pedunculated colonic polyps (LNPCPs). However, its efficacy and cost effectiveness, are limited by recurrence and the necessity for scheduled surveillance. Consequently, current surveillance intervals are conservative. Margin thermal ablation (MTA) after EMR for LNPCPs has dramatically reduced the incidence of recurrence at first surveillance colonoscopy at six-months (SC1). If this effect is durable, then subsequent surveillance intervals in patients who have been cleared of synchronous polyps could be substantially lengthened. We prospectively evaluated long-term surveillance outcomes in a cohort of LNPCPs that have undergone MTA.

Aims & Methods

Consecutive patients with LNPCPs undergoing EMR and MTA from four academic endoscopy centres were prospectively recruited. All patients that underwent successful endoscopic resection received SC1 six months post resection. EMR scars were carefully evaluated with high-definition white light, narrow band imaging with near focus and biopsy. In the absence of recurrence, second surveillance (SC2) colonoscopy was conducted at a subsequent interval of 12 months with the scar evaluation process repeated. The primary outcome was recurrence at SC2 in all LNPCPs with a recurrence-free scar at SC1.

Results

1324 LNPCPs referred for EMR were enrolled over 90 months until October 2022. Following exclusions, 1163 LNPCPs underwent EMR with complete MTA. 856 LNPCPs underwent SC1. 32 additional synchronous LNPCPs were cleared at this procedure. 25/856 (2.9%) (95%CI 1.9-4.3%) LNPCPs demonstrated recurrence. 469 LNPCPs free of recurrence at SC1 (median size 35mm) underwent SC2 at a mean interval of 22.9 months (95%CI 21.9-23.95) after the index EMR. 468 demonstrated a bland scar without recurrence. Only one recurrence occurred (0.2% 95%CI 0-1.2%), related to a 0-IIa+Is 20mm granular TVA located on the ileocaecal valve.

Conclusion

LNPCPs that have undergone successful EMR with MTA and are free of recurrence at SC1 are very unlikely to develop recurrence in subsequent surveillance out to 2 years. Following EMR of LNPCPs with MTA, patients who are cleared of synchronous neoplasia and demonstrate no recurrence after careful scar examination, can potentially undergo next surveillance in 3-5 years. Such an approach would reduce costs and enhance patient compliance.

Disclosure

Michael Bourke: Research Support: Olympus Medical, Cook Medical, Boston Scientific
The remaining authors have no financial, professional, or personal conflicts of interest to disclose

Introduction

Hot endoscopic mucosal resection (H-EMR) is the standard of care for large non-pedunculated colorectal polyps (LNPCPs) without suspicion of submucosal invasion, achieving low recurrence rates after en bloc resection or piecemeal resection with margin ablation in expert centers.^1,2 However, electrocautery is also responsible for complications which can lead to significant morbidity and necessitate additional invasive procedures.^3,4 Cold snare polypectomy (CSP) has proven to be preferable to H-EMR for adenomas ≤10mm and non-dysplastic sessile serrated lesions, providing comparable efficacy with improved safety, shorter procedural time and lower costs.⁵ These advantages have driven interest in expanding CSP to larger polyps.

Aims & Methods

This meta-analysis of randomized controlled trials (RCTs) aimed to compare the risk of recurrence and adverse events between cold snare polypectomy (CSP) and hot-endoscopic mucosal resection (H-EMR) for large non-pedunculated colorectal polyps (LNPCPs).
A systematic search of Medline, Embase and Cochrane Library databases was performed through August 2024 for studies comparing recurrence, bleeding and perforation rates between CSP and H-EMR for LNPCPs ≥15mm (PROSPERO ID: CRD42024568272). RCTs were included in the quantitative analysis. A random-effects meta-analysis, with heterogeneity measured with I², was conducted to generate pooled risk ratios (RR) with 95% confidence intervals.

Results

Four RCTs comprising 1516 LNPCPs (766 CSP and 750 H-EMR) in 1442 patients were included in the quantitative analysis. CSP demonstrated a higher recurrence risk at first surveillance colonoscopy than H-EMR in the pooled analysis (22.6% vs. 10.8%; RR=1.98; 95% CI: 1.22–3.21; p=0.02; moderate-certainty evidence), corresponding to a number needed to harm of 9. Regarding adverse events, CSP demonstrated a 67% reduced risk of delayed bleeding (1.2% vs. 3.9%; RR=0.33; 95% CI: 0.12-0.89; p=0.03; high-certainty evidence), corresponding to a number needed to treat of 37. Although CSP appeared to reduce the risk of intraprocedural bleeding (10.0% vs. 19.8%; RR=0.30, 95% CI: 0-52256.34, p=0.42), the wide confidence interval from the random-effects model included 1. There were no intraprocedural or delayed perforations in the CSP group.

Author	Study design	Number of patients		Age, mean (SD), years	Female, %	Number of LNPCPs		LNPCP size, mean/median (SD/IQR), mm	Right Location, %		Adenomatous histology, %
		CSP	H-EMR			CSP	H-EMR		CSP	H-EMR	CSP	H-EMR
O’ Sullivan T. et al., 2024	Single center, RCT	87	90	68.2 (10.0)	46.9	87	90	30 (25-35)	96.5	86.7	100	100
Steinbrück et al., 2024	Multicenter, RCT	184	192	65.9 (10.5)	48.2	193	203	30.1 (10.2)	88.1	86.2	60.7	68.5
Pohl H. et al., 2024	Multicenter, RCT	336	324	65.3 (10.2)	47.7	371	343	30 (25.4)	82.5	83.4	NR	NR
Nogales et al., 2023	Multicenter, RCT	115	114	67.9 (10.6)	43.3	115	114	25 (22-30)	80.0	78.1	71.9	77.2

Table 1. Patients, LNPCPs and procedure characteristics of the randomized controlled trials included in the quantitative analysis. (List of abbreviations: CSP, cold snare polypectomy; H-EMR, hot endoscopic mucosal resection; IQR, interquartile range; LNPCPs, large non-pedunculated colorectal polyps; NR, not reported; SD, standard deviation; RCT, randomized controlled trial)

Conclusion

CSP has nearly double the recurrence risk of H-EMR for LNPCPs. However, its superior safety profile may make it a preferable option for patients where procedural safety is prioritized over radicality, such as those with extensive comorbidities.

References

1. Ferlitsch M, Hassan C, Bisschops R et al. Colorectal polypectomy and endoscopic mucosal resection: European Society of Gastrointestinal Endoscopy (ESGE) Guideline - Update 2024. Endoscopy 2024; 56: 516-545. doi:10.1055/a-2304-3219
2. Kaltenbach T, Anderson JC, Burke CA et al. Endoscopic Removal of Colorectal Lesions: Recommendations by the US Multi-Society Task Force on Colorectal Cancer. Am J Gastroenterol 2020; 115: 435-464. doi:10.14309/ajg.0000000000000555
3. Sidhu M, Shahidi N, Gupta S et al. Outcomes of Thermal Ablation of the Mucosal Defect Margin After Endoscopic Mucosal Resection: A Prospective, International, Multicenter Trial of 1000 Large Nonpedunculated Colorectal Polyps. Gastroenterology 2021; 161: 163-170.e163. doi:10.1053/j.gastro.2021.03.044
4. Meulen LWT, Bogie RMM, Winkens B et al. Thermal ablation of mucosal defect margins to prevent local recurrence of large colorectal polyps: a systematic review and meta-analysis. Endosc Int Open 2022; 10: E1127-e1135. doi:10.1055/a-1869-2446
5. Rex DK, Anderson JC, Pohl H et al. Cold versus hot snare resection with or without submucosal injection of 6- to 15-mm colorectal polyps: a randomized controlled trial. Gastrointest Endosc 2022; 96: 330-338. doi:10.1016/j.gie.2022.03.006

Introduction

Endoscopic Mucosal Resection (EMR) with Margin Thermal Ablation by Snare-tip Soft Coagulation (MTA) is effective to treat Large (>20mm) Non-Pedunculated Colorectal Polyps (LNPCP) with recurrence in large studies at <2%. Non-lifting LNPCP (NL-LNPCP) account for approximately 10% of LNPCP and are well managed by EMR with adjunctive Cold-forceps Avulsion with adjuvant Snare-Tip soft coagulation (CAST) for non-lifting areas, however recurrence occurs in >10%. We sought to evaluate the effect of MTA on NL-LNPCPs treated by EMR and CAST.

Aims & Methods

Prospective observational data on consecutive patients with NL-LNPCPs treated by EMR and CAST at a single tertiary center was evaluated. Two cohorts were established: the pre-MTA period (January 2012-June 2017) and the MTA period, (July 2017-October 2023). The primary outcome was the comparison of recurrence rates between the two groups at first surveillance colonoscopy at 6 months (SC1).

Results

From January 2012 to October 2023, 298 NL-LNPCPs in 298 patients (median age 69.1 years, interquartile range [IQR] 61.5-76.7 years, 43.4% male) underwent EMR and CAST (median size 36.0mm, IQR 24.7-54.2mm): 72 lesions pre-MTA and 226 with MTA. The MTA cohort had a higher rate of NL-LNPCP in complex locations (ileocecal valve, ano-rectal junction, appendiceal orifice) (18.6% vs 5.6%, p=0.02), granular lesions (61.9% vs 41.7%, p=0.01), and lesions with submucosal fibrosis (87.2% vs 72.2%, p=0.05). No differences were observed in procedural time. At SC1, recurrence was lower in the MTA cohort compared to the pre-MTA cohort (2.7% vs 9.7%, p<.001). Deep mural injury type III-V (4.4% vs 4.2%, p=.93) and post-procedural bleeding (5.3 vs 4.2%, p=.94) was similar between the MTA and pre-MTA cohort respectively. There was one case of delayed perforation in the pre-MTA group.

	EMR + CAST overall cohort n=298	EMR + CAST with no STSC margins n=72	EMR + CAST with STSC margins n=226	P value
Age, median (IQR) (years)	69.1 (61.5-76.7)	68.8 (61.0-76.6)	69.3 (59.5-79.1)	.76
Size of NL-LSL, median (IQR) (mm)	36.0 (24.7-54.2)	35.8 (26.7-44.9)	36.8 (23.5-50.1)	.59
Complex location (ileocecal valve, anorectal junction, appendiceal orifice) (n,%)	46 (15.4)	4 (5.6)	42 (18.6)	.02
Morphology, (n,%) Granular Non-Granular Mixed Consistent with SSL Unable to be classified	170 (57.0) 101 (33.9) 13 (4.4) 4 (1.3) 10 (3.4)	30 (41.7) 31 (43.0) 3 (4.2) 3 (4.2) 5 (6.9)	140 (61.9) 70 (31.1) 10 (4.4) 1 (0.4) 5 (2.2)	.01
Procedure duration, median (IQR) (min)	44.2 (23.8-64.7)	39.8 (17.8-61.8)	45.6 (21.6-69.6)	.38
Submucosal fibrosis (n,%)	249 (83.6)	52 (72.2)	197 (87.2)	.05
Delayed bleeding (n,%)	15 (5.0)	3 (4.2)	12 (5.3)	.94
Delayed perforation (n,%)	1 (0.3%)	1 (1.4)	0 (0)	.09
Recurrence at first follow-up (n,%)	13/216 (4.4)	7/66 (9.7)	6/150 (2.7)	<.001

Conclusion

The implementation of MTA significantly reduced recurrence at SC1 for NL-LNPCP treated by EMR with CAST. The refinement of CAST and addition of MTA in recent years has enabled the treatment of more complex lesions with greater effectiveness without compromising safety.

Introduction

Endoscopic mucosal resection (EMR) of large (>/-20mm) non-pedunculated colorectal polyps (LNPCP) </- 40mm is associated with an increased risk of recurrent or residual adenoma (RRA). Margin Thermal Ablation to the EMR defect margin using snare-tip soft coagulation (MTA) reduces the rate of RRA. We sought to analyse its effect in a large prospective cohort of LNPCP >/-40mm.

Aims & Methods

We retrospectively analysed a prospectively collected cohort of consecutive patients who underwent EMR in an expert tissue resection centre. MTA technique was developed in 2012. Enrolment for the MTA randomised control occurred between July 2013-May 2016 and became standard practice from mid-2017. The cohort was divided into three phases: ‘pre-MTA’; April 2008- June 2012, ‘MTA adoption’; July 2012-June 2017 and ‘standardised MTA’; July 2017-April 2023. The primary outcome was to compare the RRA rate between the three time periods.

Results

Over 15 years until April 2023, 973 LNPCP >/-40mm in 973 patients underwent EMR (median lesion size 50mm, IQR 20mm) of which 893 (92%) were successful. 824 patients (median lesion size 50mm, IQR 20) underwent SC1 (median of 6 months [IQR 4]). The rates of RRA in the pre-MTA, MTA-adoption and standardised-MTA phases were 20.3% (n=45/221), 19.1% (n=59/309) and 4.4% (n=13/294) respectively (p=<0.001). The rates of complete MTA in the pre-MTA, MTA adoption and standardised-MTA phases were 0, 38.2% (n=118/309) and 93.9% (n=276/294). 18 (6.1%) of cases within the standardised-MTA did not receive MTA due to difficult access (n=7), concern for stricture formation in fully circumferential LNPCP (n=9) or sedation-related issues (n=2). The rate of RRA in this group was 22.2% (n=4/18).

	Pre-MTA N=221	MTA-adoption N=309	Standardised-MTA N=294	p
Age, years median (IQR)	69 (16)	69 (15)	67 (15)	0.06
Lesion size, mm median (IQR)	50 (20)	50 (20)	50 (20)	0.17
Location n (%) Right*	123 (55.7)	165 (53.4)	163 (55.4)	0.85
Left	98	144	131
RRA n (%)	45 (20.3)	59 (19.1)	13 (4.4)	<0.001
Complete MTA n (%)	0	118 (38.2)	276 (93.9)	<0.001
RRA in MTA Cohort n (%)	NA	3 (2.5)	9 (3.3)	<0.001
RRA in no MTA Cohort n (%)	45 (20.3)	56 (29.3)	4 (22.2)	0.11

*The right colon was defined as proximal to the splenic flexure

Conclusion

MTA post-EMR of LNPCP >/-40mm (median size 50mm) significantly reduced the rate of RRA in a large, prospective cohort. When MTA was not applied, RRA was similar across the three time periods (p=0.1), indicating that the main impact on RRA reduction was the use of MTA with snare-tip soft coagulation, rather than a factor of EMR technique improvement over time.